Salmonella is the most common cause of foodborne illness with lethal outcome in the US. The ability of Salmonella to consistently contaminate the US food supply creates an urgent need for better understanding of the molecular mechanism that allow this pathogen to persist successfully in food producing animals thus representing a significant source of Salmonella for humans. The first specific aim of this proposal is to evaluate the role of factors present in the intestinal tract that affect S. typhimurium gene expression. The calf ligated ileal loop model and a S. typhimurium microarray will be used to evaluate alterations in S. typhimurium gene expression in response to the intestinal envrionment. The second specific aim is to evaluate the role of post-transcriptional regulation in S. typhimurium gene expression in the intestine by measuring the levels of proteins associated with regulatory pathways identified in the first specific aim. The third specific aim is to evaluate the molecular mechanisms by which the conditions of the intestinal lumen and epithelium alter the virulence and persistence of S. typhimurium in the calf model of enterocolitis. These experiments will offer new insight into the requirements of Salmonella in the intestinal tract and may offer potential innovative approaches to safeguard human health. Dr. Lawhon completed her D.V.M. at Texas A&M University College of Veterinary Medicine in May 1997. She completed her Ph.D. in the laboratory of Dr. Craig Altier, identifying the effect of intestinal short-chain fatty acids on Salmonella invasion gene regulation. Having a strong interest in bacterial pathogenesis and in veterinary medicine, Dr. Lawhon's career goal is to become an independent investigator at the interface between these two areas. The research collaboration between Dr. B[unreadable]umler in the Texas A&M Health Science Center and Dr. Adams in the College of Veterinary Medicine provides a unique opportunity to achieve this career goal.